1. Technical Field
The present invention relates, in general, to a method of controlling the growth of a virus and, in particular, to a method of controlling viral growth by causing a viral gene product, or derivative thereof, to be produced in a permissive host in a manner that results in disruption of the vital life cycle.
2. Background Information
Viral infection of a host cell commences with attachment of the virus to the cell surface and subsequent penetration of the genetic material of the virus (DNA or RNA) into the cytoplasm of the host cell. The viral genetic material crosses the plasma membrane of the cell either alone or in association with inner viral proteins. The DNA of most animal viruses is eventually found in the cell nucleus where it can interact with the host cell's nucleic acid synthesizing machinery to produce viral mRNA. This mRNA is then transported to the cytoplasm where viral proteins are synthesized. The vital protein products are used in the construction of new virus particles. Completed viral particles are released either upon rupture of the infected host cell or by gradual exocytosis via intracellular transport systems. Release of the viral particles completes one cycle of the lytic stage of vital growth.
A second stage of vital growth, displayed by certain viruses, is the latent phase. During this stage, viral DNA is stably maintained in the nucleus and is replicated as the host cell grows and divides. While many DNA viruses become integrated into the host chromosome, others are maintained extrachromosomally. In the case of retroviruses, a cDNA is transcribed from the retroviral RNA template and subsequently integrated into the host genome. In response to ill-defined "inducing events", viral DNA can emerge from its latent state and again enter the lytic cycle.
Central to viral infection and growth are:
1) the temporal expression of viral genes in response to specific viral regulators, and 2) the specific and ordered interaction of the products of that gene expression. Recent developments in molecular genetics and gene transfer techniques have made it possible to study the mechanisms underlying both of these aspects of virus production. The use of these same techniques to impart viral resistance has proven successful in plants. Specifically, insertion of a cDNA of Tobacco Mozaic Virus (TMV) coat protein gene results both in the expression of that protein at a level of approximately 0.1% of the total leaf protein of the transgenic tobacco and in the acquisition of resistance to infection by TMV (Able et al Science 232:738 (1986)). The ability to confer viral resistance on animals, either by direct gene transfer or germ line transformation, would provide a new and powerful tool for use in the prevention and treatment of specific types of viral infections. PA1 i) introducing into the host cell a virus-related gene encoding a product capable of specifically interacting, directly or indirectly, with the genome of the infecting virus (or a product encoded therein) so that the life cycle of the infecting virus is disrupted; and PA1 ii) causing expression of the virus-related gene and interaction of the product of that expression with the genome of the infecting virus (or product encoded therein). PA1 i) introducing into the cell a virus-related gene encoding a product capable of specifically interacting with the genome of the infecting virus (or product encoded therein) so that the life cycle of the infecting virus is disrupted; and PA1 ii) causing expression of the virus-related gene and interaction of the product of that expression with the genome of the infecting virus (or product encoded therein).